Limited data support how to safely and effectively treat refractory pain and agitation in neonates and infants. Gabapentin has been used in this patient population and has shown promising results, yet there is still a paucity of data about its clinical efficacy. There is a need for a larger evaluation to determine its effectiveness. This study describes one institution's experience with gabapentin for the treatment of refractory pain and agitation in the neonatal intensive care unit (NICU). This was a retrospective, observational evaluation of patients who received gabapentin in the level IV NICU at the Cleveland Clinic Children's Hospital. Changes in neonatal pain, agitation, and sedation scale (N-PASS) scores and analgesic and sedative medication requirements were analyzed, as were gabapentin dose requirements and adverse reactions. Between January 2012 and November 2015, 22 patients received gabapentin and were included in this study. The average gabapentin starting dose was 10.2 mg/kg/day, with maximum doses up to 25.5 mg/kg/day. The median N-PASS score at gabapentin therapy initiation was 3.1 and after gabapentin initiation the last N-PASS score documented was 0 in all but 5 patients. Gabapentin use reduced the need for analgesic or sedative medications. The drug was well tolerated, and only 1 patient experienced an adverse reaction to gabapentin (i.e., nystagmus). Gabapentin was well tolerated and associated with decreases in pain scores. It's use resulted in decreased requirements for analgesic and sedative medications. Gabapentin therapy appears to be an effective option for neonates and infants with refractory pain and agitation.